Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC
IL-6 and IL-17 are paradoxical cytokines that progress inflammatory states in chronic diseases, including cancer. In lung cancer, their role has been elucidated to favor cancer development by modulating signaling mechanisms critical to cellular growth. The intrinsic ability of these cytokines to inf...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/25/2/1216 |
| _version_ | 1797339740315320320 |
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| author | Riya Khilwani Shailza Singh |
| author_facet | Riya Khilwani Shailza Singh |
| author_sort | Riya Khilwani |
| collection | DOAJ |
| description | IL-6 and IL-17 are paradoxical cytokines that progress inflammatory states in chronic diseases, including cancer. In lung cancer, their role has been elucidated to favor cancer development by modulating signaling mechanisms critical to cellular growth. The intrinsic ability of these cytokines to influence macroautophagy is yet another reason to facilitate lung cancer. Here, we employed a systems immunology approach to discover the mechanistic role of these cytokines in cancer development. In a biological system, at later stages, the activation of NFkB stimulates immunosuppressive phenotypes to achieve tolerating effects in a transformed cell. We found that the upregulation of cytokines signaled M2 macrophages to modulate tumor responses through the activation of autophagic intermediates and inflammasome mediators. This caused immune perturbations in the tumor microenvironment, which were associated with cancer inflammation. To address these inflammatory states, we performed triggered event analysis to examine whether overexpressing immune effectors or downregulating immune suppressors may have an effect on cancer reversal. Interestingly, the inhibition of immune regulators opposed the model outcome to an increased immune response. Therefore, IL6-IL17-mediated regulation of lung cancer may address tumor malignancy and potentiate the development of newer therapeutics for NSCLC. |
| first_indexed | 2024-03-08T09:52:44Z |
| format | Article |
| id | doaj.art-4b7636dc9a6f477387b63903c6900427 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-08T09:52:44Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4b7636dc9a6f477387b63903c69004272024-01-29T13:58:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672024-01-01252121610.3390/ijms25021216Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLCRiya Khilwani0Shailza Singh1Systems Medicine Laboratory, National Centre for Cell Science, NCCS Complex, Ganeshkhind, SPPU Campus, Pune 411007, IndiaSystems Medicine Laboratory, National Centre for Cell Science, NCCS Complex, Ganeshkhind, SPPU Campus, Pune 411007, IndiaIL-6 and IL-17 are paradoxical cytokines that progress inflammatory states in chronic diseases, including cancer. In lung cancer, their role has been elucidated to favor cancer development by modulating signaling mechanisms critical to cellular growth. The intrinsic ability of these cytokines to influence macroautophagy is yet another reason to facilitate lung cancer. Here, we employed a systems immunology approach to discover the mechanistic role of these cytokines in cancer development. In a biological system, at later stages, the activation of NFkB stimulates immunosuppressive phenotypes to achieve tolerating effects in a transformed cell. We found that the upregulation of cytokines signaled M2 macrophages to modulate tumor responses through the activation of autophagic intermediates and inflammasome mediators. This caused immune perturbations in the tumor microenvironment, which were associated with cancer inflammation. To address these inflammatory states, we performed triggered event analysis to examine whether overexpressing immune effectors or downregulating immune suppressors may have an effect on cancer reversal. Interestingly, the inhibition of immune regulators opposed the model outcome to an increased immune response. Therefore, IL6-IL17-mediated regulation of lung cancer may address tumor malignancy and potentiate the development of newer therapeutics for NSCLC.https://www.mdpi.com/1422-0067/25/2/1216IL-6IL-17NSCLCNFkBM2 macrophagessystems immunology |
| spellingShingle | Riya Khilwani Shailza Singh Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC International Journal of Molecular Sciences IL-6 IL-17 NSCLC NFkB M2 macrophages systems immunology |
| title | Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC |
| title_full | Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC |
| title_fullStr | Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC |
| title_full_unstemmed | Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC |
| title_short | Traversing through the Mechanistic Event Analysis in IL-6 and IL-17 Signaling for a New Therapeutic Paradigm in NSCLC |
| title_sort | traversing through the mechanistic event analysis in il 6 and il 17 signaling for a new therapeutic paradigm in nsclc |
| topic | IL-6 IL-17 NSCLC NFkB M2 macrophages systems immunology |
| url | https://www.mdpi.com/1422-0067/25/2/1216 |
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